Cluster Analysis of Inflammatory Biomarker Expression in the International Severe Asthma Registry

Denton, Eve; Price, David; Tran, Trung; Canonica, Giorgio Walter; Menzies‐Gow, Andrew; FitzGerald, J. Mark; Sadatsafavi, Mohsen; Llano, Luís Pérez de; Christoff, George; Quinton, Anna; Rhee, Chin Kook; Brusselle, Guy; Ulrik, Charlotte Suppli; Lugogo, Njira L; Hore‐Lacy, Fiona; Chaudhry, Isha; Bulathsinhala, Lakmini; Murray, Ruth; Carter, Victoria A.; Hew, Mark

doi:10.1016/j.jaip.2021.02.059

Cited by 71 publications

(78 citation statements)

References 28 publications

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“…Despite the IgE ≥ 75 IU/mL threshold was recently used in the clustering of severe asthma [ 29 ] and IgE ≥ 100 IU/mL has been covered in the definition of T2-high allergic inflammation [ 19 ], we deliberately ruled out the serum total IgE content from our patients’ stratification. Total IgE levels have been independently associated, in non-atopic individuals, with cigarette smoking and alcohol consumption, while variable concentrations have also been detected in aging, autoimmunity, immunodeficiency (e.g., Job’s Syndrome), cancer, obesity, parasitic infection, and metabolic syndrome [ 30 ]; otherwise, allergic patients may have low total IgE levels.…”

Section: Discussionmentioning

confidence: 99%

Characterization of T2-Low and T2-High Asthma Phenotypes in Real-Life

et al. 2021

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Asthma is a heterogeneous and complex condition characterized by chronic airway inflammation, which may be clinically stratified into three main phenotypes: type 2 (T2) low, T2-high allergic, and T2-high non-allergic asthma. This real-world study investigated whether phenotyping patients with asthma using non-invasive parameters could be feasible to characterize the T2-low and T2-high asthma phenotypes in clinical practice. This cross-sectional observational study involved asthmatic outpatients (n = 503) referring to the Severe Asthma Centre of the San Luigi Gonzaga University Hospital. Participants were stratified according to the patterns of T2 inflammation and atopic sensitization. Among outpatients, 98 (19.5%) patients had T2-low asthma, 127 (25.2%) T2-high non-allergic, and 278 (55.3%) had T2-high allergic phenotype. In comparison to T2-low, allergic patients were younger (OR 0.945, p < 0.001) and thinner (OR 0.913, p < 0.001), had lower smoke exposure (OR 0.975, p < 0.001) and RV/TLC% (OR 0.950, p < 0.001), higher prevalence of asthma severity grade 5 (OR 2.236, p < 0.05), more frequent rhinitis (OR 3.491, p < 0.001) and chronic rhinosinusitis with (OR 2.650, p < 0.001) or without (OR 1.919, p < 0.05) nasal polyps, but less common arterial hypertension (OR 0.331, p < 0.001). T2-high non-allergic patients had intermediate characteristics. Non-invasive phenotyping of asthmatic patients is possible in clinical practice. Identifying characteristics in the three main asthma phenotypes could pave the way for further investigations on useful biomarkers for precision medicine.

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Section: Discussionmentioning

confidence: 99%

Characterization of T2-Low and T2-High Asthma Phenotypes in Real-Life

et al. 2021

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“…Yet clinical studies show wide heterogeneity to asthma both across the life course and at different levels of asthma severity. 25 , 80–82 …”

Section: The Treatable Traits Paradigm – Difficult-to-control Asthma As a Multimorbidity Difficult Breathing Syndromementioning

confidence: 99%

“…Obesity is highly prevalent among difficult asthma populations 23 , 25 , 80 and is associated with worse asthma severity. 137 The negative impact of obesity on asthma may be part-mediated by mechanical effects on lung function.…”

Section: The Treatable Traits Paradigm – Difficult-to-control Asthma As a Multimorbidity Difficult Breathing Syndromementioning

confidence: 99%

“…Yet clinical studies show wide heterogeneity to asthma both across the life course and at different levels of asthma severity. 25,[80][81][82] It is also clear that a proportion of patients with asthma do not attain good asthma control with current treatments. This failure to deliver good asthma control with current approaches was the focus of a Lancet 2017 Commission "After asthma: redefining airways disease".…”

Section: The Treatable Traits Paradigm -Difficult-to-control Asthma As a Multimorbidity Difficult Breathing Syndromementioning

confidence: 99%

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Recent Insights into the Management of Inflammation in Asthma

Rupani¹,

Fong²,

Kyyaly³

et al. 2021

JIR

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The present prevailing inflammatory paradigm in asthma is of T2-high inflammation orchestrated by key inflammatory cells like Type 2 helper lymphocytes, innate lymphoid cells group 2 and associated cytokines. Eosinophils are key components of this T2 inflammatory pathway and have become key therapeutic targets. Real-world evidence on the predominant T2-high nature of severe asthma is emerging. Various inflammatory biomarkers have been adopted in clinical practice to aid asthma characterization including airway measures such as bronchoscopic biopsy and lavage, induced sputum analysis, and fractional exhaled nitric oxide. Blood measures like eosinophil counts have also gained widespread usage and multicomponent algorithms combining different parameters are now appearing. There is also growing interest in potential future biomarkers including exhaled volatile organic compounds, micro RNAs and urinary biomarkers. Additionally, there is a growing realisation that asthma is a heterogeneous state with numerous phenotypes and associated treatable traits. These may show particular inflammatory patterns and merit-specific management approaches that could improve asthma patient outcomes. Inhaled corticosteroids (ICS) remain the mainstay of asthma management but their use earlier in the course of disease is being advocated. Recent evidence suggests potential roles for ICS in combination with long-acting beta-agonists (LABA) for as needed use in mild asthma whilst maintenance and reliever therapy regimes have gained widespread acceptance. Other anti-inflammatory strategies including ultra-fine particle ICS, leukotriene receptor antagonists and macrolide antibiotics may show efficacy in particular phenotypes too. Monoclonal antibody biologic therapies have recently entered clinical practice with significant impacts on asthma outcomes. Understanding of the efficacy and use of those agents is becoming clearer with a growing body of real-world evidence as is their potential applicability to other treatable comorbid traits. In conclusion, the evolving understanding of T2 driven inflammation alongside a treatable traits disease model is enhancing therapeutic approaches to address inflammation in asthma.

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“…In fact, this parameter has shown less consistent results across different studies [ 99 , 100 , 101 , 102 ]. In any case, FeNO and eosinophilic inflammation in the bronchi may have at least partially distinct pathways and disease expression, although both can be markers of T2-high asthma phenotype/endotype [ 10 , 103 ].…”

Section: Assessment Of Metabolic Changes In Inflammatory Asthma Phenotypesmentioning

confidence: 99%

Metabolic Phenotypes in Asthmatic Adults: Relationship with Inflammatory and Clinical Phenotypes and Prognostic Implications

et al. 2021

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Bronchial asthma is a chronic disease that affects individuals of all ages. It has a high prevalence and is associated with high morbidity and considerable levels of mortality. However, asthma is not a single disease, and multiple subtypes or phenotypes (clinical, inflammatory or combinations thereof) can be detected, namely in aggregated clusters. Most studies have characterised asthma phenotypes and clusters of phenotypes using mainly clinical and inflammatory parameters. These studies are important because they may have clinical and prognostic implications and may also help to tailor personalised treatment approaches. In addition, various metabolomics studies have helped to further define the metabolic features of asthma, using electronic noses or targeted and untargeted approaches. Besides discriminating between asthma and a healthy state, metabolomics can detect the metabolic signatures associated with some asthma subtypes, namely eosinophilic and non-eosinophilic phenotypes or the obese asthma phenotype, and this may prove very useful in point-of-care application. Furthermore, metabolomics also discriminates between asthma and other “phenotypes” of chronic obstructive airway diseases, such as chronic obstructive pulmonary disease (COPD) or Asthma–COPD Overlap (ACO). However, there are still various aspects that need to be more thoroughly investigated in the context of asthma phenotypes in adequately designed, homogeneous, multicentre studies, using adequate tools and integrating metabolomics into a multiple-level approach.

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Cluster Analysis of Inflammatory Biomarker Expression in the International Severe Asthma Registry

Cited by 71 publications

References 28 publications

Characterization of T2-Low and T2-High Asthma Phenotypes in Real-Life

Characterization of T2-Low and T2-High Asthma Phenotypes in Real-Life

Recent Insights into the Management of Inflammation in Asthma

Metabolic Phenotypes in Asthmatic Adults: Relationship with Inflammatory and Clinical Phenotypes and Prognostic Implications

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